Emerging Role of HDACs in Regeneration and Ageing in the Peripheral Nervous System: Repair Schwann Cells as Pivotal Targets


Type
Article
Change log
Authors
Gomez-Sanchez, Jose Antonio 
Patel, Nikiben 
Martirena, Fernanda 
Fazal, Shaline V 
Mutschler, Clara 
Abstract

The peripheral nervous system (PNS) has a remarkable regenerative capacity in comparison to the central nervous system (CNS), a phenomenon that is impaired during ageing. The ability of PNS axons to regenerate after injury is due to Schwann cells (SC) being reprogrammed into a repair phenotype called Repair Schwann cells. These repair SCs are crucial for supporting axonal growth after injury, myelin degradation in a process known as myelinophagy, neurotropic factor secretion, and axonal growth guidance through the formation of Büngner bands. After regeneration, repair SCs can remyelinate newly regenerated axons and support nonmyelinated ax-ons. Increasing evidence points to an epigenetic component in the regulation of repair SC gene ex-pression changes, which is necessary for SC reprogramming and regeneration. One of these epigenetic regulations is histone acetylation by histone acetyl transferases (HATs) or histone deacetylation by histone deacetylases (HDACs). In this review, we have focused particularly on three HDAC classes (I, II, and IV) that are Zn2+-dependent deacetylases. These HDACs are important in repair SC biology and remyelination after PNS injury. Another key aspect explored in this review is HDAC genetic compensation in SCs and novel HDAC inhibitors that are being studied to improve nerve regeneration.

Description
Keywords
HDACs, HDACs therapies, Schwann cell, ageing, myelin, nerve injury, nerve regeneration, remyelination, repair Schwann cell, Axons, Histone Deacetylases, Histones, Nerve Regeneration, Peripheral Nervous System, Schwann Cells
Journal Title
International Journal of Molecular Sciences
Conference Name
Journal ISSN
1422-0067
1422-0067
Volume Title
23
Publisher
MDPI AG
Sponsorship
Medical Research Council (2251399)
Ministerio de Economía y Competitividad (BFU2016-75864R and PID2019-109762RB-I00) ISABIAL (UGP18-257 and UGP-2019-128) Conselleria Educació Generalitat Valenciana (PROMETEO 2018/114) Medical Research Council (UK) studentship (2251399)